The principal investigators have worked separately on two experimental modes that result in a marked increase in renal phospholipid synthesis. A combined comparative study of the sequence of events that characterize the changes related to these metabolic alterations is proposed, using the skills and facilities available and extending the collaboration to include individuals with interests in basic aspects of this phenomenon. The combined ultrastructural and biochemical change of the renal medullary area during potassium (K) depletion was first described and has been extensively studied by one investigator (BHS). This model combines a predominantly medullary lesion with a marked increase in tissue phospholipid and a massive new membrane formation in a unique lysosomal structure that fills all cells. An associated zonal hyperplasia occurs. The second model consists of metabolic and structural changes of renal compensatory growth after uninephrectomy in rats. Predominantly cortical changes have been observed with proportional increases in structural components. The sequence of events which characterize new cellular membrane production can be described by making measurements at various times after onset of K-depletion and uninephrectomy. High resolution electron microscopy will be employed to characterize the sequence of cellular membrane changes in cortex and medulla which accompany the appearance of new organelles in K-depletion and in renal compensatory growth. These observations will be correlated with measurements of renal phospholipid synthesis and turnover in the same animals. The findings from the proposed study will enhance understanding of new membrane production in response to a pathological stimulus (K-depletion) and a physiological stimulus (uninephrectomy) in the two tissues of the same organ (cortex and medulla). The results will clarify the effects of K-depletion on renal cortical and medullary tissue, and is an appropriate model for study of the K-depletion nephropathy in man. BIBLIOGRAPHIC REFERENCE: Toback, F. G., Ordonez, N. G., Bortz, S. L., and Spargo, B. H.: Zonal changes in renal structure and phospholipid metabolism in potassium-deficient rats. Lab. Invest. 34: 115-124, 1976.